Many cellular injuries, such as exposure to ionizing radiation, result in the production of reactive oxygen species (ROS). These ROS produce a spectrum of damage via multiple mechanisms including membrane destabilization, mitochondrial disruption, and metabolic derangement. Furthermore, these ROS may activate endonucleases by inducing their synthesis and release from cellular compartments, thereby, allowing nuclear import of endonucleases and DNA degradation. DNA damage induced by endonucleases is several orders of magnitude greater than the direct damage by ROS. The peak of endonuclease activity usually follows oxidative stress by several hours, induces apoptotic cell death, and then declines in a few days.
While there are native antioxidant enzymes that convert ROS to water and oxygen, these systems are not always sufficient, however. Thus, there is a need for strategies to augment these systems and provide greater protection. Furthermore, there are currently no pharmaceutical compositions that directly target and inhibit cell death endonucleases. Thus, there is a current need for compositions that have the ability to inhibit the activity of cell death endonucleases by a variety of mechanisms.